Finally, it is also possible that the decrease in tumor burden in bone is due to an effect of bisphosphonates on angiogenesis [ 35].
More work is needed to determine whether bisphosphonates truly have antitumor activity in humans, or whether the reduction in tumor burden in bone is due to the reduction of bone-derived growth factors released into the local microenvironment as a consequence of inhibiting osteoclastic bone resorption.
In animal models of metastatic disease, BPs have been shown to slow the development of bone metastases and to reduce tumour burden in bone (Wingen et al, 1986; Yoneda et al, 2000).
Inhibition of bone resorption either by bisphosphonate (BP) treatment or by blocking RANKL signalling with osteoprotegerin (OPG) has been shown to reduce tumour burden in bone and inhibit bone destruction in murine xenograft models of breast cancer.
BSI calculation using EXINIboneBSI is an objective fully automated approach to quantify skeletal tumor burden in bone scans.
The ability of ZA to decrease the cancer burden in bone is understandable, given its high concentration and long half-life in the bone environment.
Taken together, these results indicate that bisphosphonates may exert direct growth inhibitory effects on breast cancer cells, leading to reduced metastatic tumour burden in bone.
Based on the ability of OPG to prevent osteolysis and reduce CaP tumor burden in bone, we hypothesize that CaP-derived factor(s) induce the production of RANKL within bone, which then culminates in local osteolysis and the stimulation of tumor growth.
Notably, mice treated with zoledronic acid showed significantly lower leukemia burden in bone marrow, spleen and blood, as well as higher numbers of normal bone marrow cells compared to control mice at Day 15 (Fig. 4g, h).
Laboratory models have shown that bisphosphonates can reduce the tumor burden in bone.
